Method for the treatment of cardiac and of vascular hypertrophy and hyperplasia

Abstract

The invention relates to a method for the treatment of cardiac and of vascular hypertrophy and hyperplasia by administration of angiotensin converting enzyme inhibitors. Administration of compounds of the formula I <IMAGE> (I) in which n is 1 or 2, R, R1, R2 and R3 are identical or different and each is hydrogen or an organic radical, and R4 and R5 form, together with the atoms carrying them, a mono-, bi- or tricyclic heterocyclic ring system, is preferred. The invention additionally relates to angiotensin converting enzyme inhibitors and to agents containing these for administration for the treatment of the abovementioned diseases.

We claim: 
     
       1. A method for the treatment of cardiac and of vascular hypertrophy and hyperplasia in mammals comprising the step of administering to a mammal an effective amount of an angiotensin converting enzyme inhibitors of the formula I ##STR8## in which n is 1 or 2, R is hydrogen, alkyl with 1-8 carbon atoms, or aryl which has 6-12 carbon atoms,   R 1  is hydrogen, an aliphatic radical with 1-6 carbon atoms, or the side-chain, which is protected where necessary, of a naturally occurring α-amino acid,   R 2  and R 3  are identical or different and are hydrogen, alkyl with 1-6 carbon atoms, aryl with 6-12 carbon atoms or (C 6  -C 12 )-aryl-(C 1  -C 4 )-alkyl, and   R 4  and R 5  form, together with the atoms carrying them, a heterocyclic mono, bi-or tri cyclic ring system with 4 to 15 carbon atoms, or a physiologically tolerated salt thereof.     
     
     
       2. A method for the treatment of cardiac and of vascular hypertrophy and hyperplasia in mammals as claimed in claim 1, wherein R 4  and R 5  form, together with the atoms carrying them, a heterocyclic bicyclic ring system from the series comprising: tetrahydroisoquinoline, decahydroisoquinoline, octahydroindole and octahydrocyclopentapyrrole. 
     
     
       3. The method as claimed in claim 1, wherein [S,S,S,S,S]-N-(1-carbethoxy-3-phenyl-propyl)-alanyl-octahydroindole-2-carboxylic acid is administered. 
     
     
       4. The method as claimed in claim 1, wherein N-[1-(S)-carbethoxy-3-phenyl-propyl-(S)-alanyl]-2S,3aR,7aS-octahydroindole-2-carboxylic acid is administered. 
     
     
       5. The method as claimed in claim 1, wherein [S,S,S,S,S]-N-[(1-carbethoxy-3-phenyl-propyl-(S)-alanyl]-decahydroisoquinoline-3-carboxylic acid is administered. 
     
     
       6. The method as claimed in claim 1, wherein [S,S,S,]-N-[(1-carbethoxy-3-phenyl-propyl)-alanyl)-tetrahydroisoquinoline-3-carboxylic acid is administered. 
     
     
       7. The method as claimed in claim 1, wherein (S,S,S,S,S)-N-(1-carbethoxy-3-phenyl-propyl)-alanyl-2-azabicyclo[3.3.0]octane-3-carboxylic acid is administered. 
     
     
       8. The method as claimed in claim 1, wherein N-(1-S-carbethoxy-3-phenyl-propyl)-S-alanyl-cis-endo-2-azabicyclo[3.1.0]hexane-3-S-carboxylic acid is administered. 
     
     
       9. The method as claimed in claim 1, wherein N-(1-S-Carbethoxy-3-phenyl-propyl)-S-alanyl-cis-endo-2,3,3a,4,5,7a-hexahydroindole-2-S-carboxylic acid is administered. 
     
     
       10. The method as claimed in claim 1, wherein, in place of the ethyl esters, the corresponding dicarboxylic acids are administered. 
     
     
       11. The method as claimed in claim 1, wherein the angiotensin converting enzyme inhibitors are administered orally or parenterally. 
     
     
       12. The method as claimed in claim 1, wherein the angiotensin converting enzyme inhibitors are combined with pharmaceutically suitable vehicles and auxiliaries for the forms appropriate for administration. 
     
     
       13. The method as claimed in claim 1 for the treatment of cardiac hypertrophy and hyperplasia. 
     
     
       14. The method as claimed in claim 1 for the treatment of vascular hypertrophy and hyperplasia.